Department of Orthopedics, the Second Xiangya Hospital of Central South University, Changsha, China.
Orthopedic Biomedical Materials Engineering Laboratory of Hunan Province, Changsha, China.
Front Endocrinol (Lausanne). 2022 Sep 14;13:975647. doi: 10.3389/fendo.2022.975647. eCollection 2022.
With the advancement of world population aging, age-related osteoporosis (OP) and sarcopenia (SP) impose enormous clinical and economic burden on society. Evidence from accumulating studies indicates that they mutually influence one another. However, an observational study may be affected by potential confounders. Meanwhile, a Mendelian randomization (MR) study can overcome these confounders to assess causality.
The aim of this study was to evaluate the causality between OP and SP, informing new strategies for prevention, diagnosis, and treatment of osteosarcopenia.
Instrumental variables (IVs) at the genome-wide significance level were obtained from published summary statistics, and the inverse variance weighted method and several other MR methods were conducted to evaluate the bi-directional causality between SP and OP. Myopia was analyzed as a negative control outcome to test the validity of IVs.
Femoral neck bone mineral density (FN BMD), lumbar spine BMD (LS BMD), and forearm BMD (FA BMD) had a direct causal effect on appendicular lean mass (ALM) [FA BMD-related analysis: odds ratio (OR) = 1.028, 95% confidence interval (CI) = (1.008,1.049), = 0.006; FN BMD-related analysis: OR (95% CI) = 1.131 (1.092,1.170), = 3.18E-12; LS BMD-related analysis: OR (95% CI) = 1.080 (1.062,1.098), = 2.86E-19]. ALM had a significant causal effect on LS BMD [OR (95% CI) = (1.033,1.147), = 0.001]. There was no evidence for causal association between BMD and low grip strength.
OP and SP might mutually have a significant causal effect on each other. Our results supported the idea that the patient with severe OP was more susceptible to lose ALM and severe ALM loss might reduce LS BMD.
随着世界人口老龄化的发展，与年龄相关的骨质疏松症（OP）和肌肉减少症（SP）给社会带来了巨大的临床和经济负担。越来越多的研究证据表明，它们相互影响。然而，观察性研究可能会受到潜在混杂因素的影响。与此同时，孟德尔随机化（MR）研究可以克服这些混杂因素，评估因果关系。
本研究旨在评估 OP 和 SP 之间的因果关系，为防治骨质疏松性肌少症提供新策略。
从已发表的汇总统计数据中获得全基因组显著水平的工具变量（IVs），并采用逆方差加权法和其他几种 MR 方法来评估 SP 和 OP 之间的双向因果关系。近视被分析为阴性对照结果，以测试 IVs 的有效性。
股骨颈骨密度（FN BMD）、腰椎 BMD（LS BMD）和前臂骨密度（FA BMD）对四肢瘦质量（ALM）有直接的因果影响[FA BMD 相关分析：比值比（OR）= 1.028，95%置信区间（CI）=（1.008,1.049）， = 0.006；FN BMD 相关分析：OR（95%CI）= 1.131（1.092,1.170）， = 3.18E-12；LS BMD 相关分析：OR（95%CI）= 1.080（1.062,1.098）， = 2.86E-19]。ALM 对 LS BMD 有显著的因果影响[OR（95%CI）=（1.033,1.147）， = 0.001]。BMD 与低握力之间没有因果关系的证据。
OP 和 SP 可能相互对彼此有显著的因果影响。我们的结果支持这样一种观点，即严重 OP 的患者更容易失去 ALM，严重的 ALM 丢失可能会降低 LS BMD。
